Myelin sheaths, elaborated in the central nervous system by oligodendrocytes, are intimately associated with the processes of neurons and act to facilitate the conduction of nerve impulses. The formation of myelin is a prominent part of the development of the nervous system, and the disruption of myelin in human neuropathological conditions such as multiple sclerosis is associated with dramatic deterioration of function. The studies proposed here are aimed at understanding the cellular mechanisms which contribute to the formation of myelin during development, and to its reformation during repair from demyelinating disease. The formation of oligodendrocytes from proliferating precursor cells is necessarily the first step in myelin formation in the central nervous system; however, the precursor cell is poorly understood. These studies will probe the biochemical indentity of the precursor cell by a combination of thymidine autoradiography and immunocytochemical staining, to determine whether the proliferating oligodendrocyte precursor cells contain the myelin specific protiens, myelin basic protein and myelin-associated glycoprotein and, if they do not, at what time after cessation of cell division these proteins appear in the developing oligodendrocytes. Furthermore, changes in immunoreactivity for myelin basic protein and myelin-associated glycoprotein will be correlated with changes in cell fine structure. The production of neuroglial cells will also be studied in two genetic disorders of mouse, quaking and shiverer, which produce excess numbers of oligodendrocytes. Study of this overproduction may give clues to the mechanisms which stimulate oligodendrocyte formation in normal development and in remyelination. The analysis proposed will establish the period of development during which the excess cells are formed in the mutants, using quantitative light and electron microscopy. Gliogenesis in the mutants wil then be examined by thymidine autoradiography and immunocytochemistry, to discover whether the overproduction of oligodendrocytes is associated with stem cells with characteristics similar to or different from those established for normal development.